Synthesis and self-assembly of DNA-β turn Conjugates

This thesis discusses the synthesis and self-assembly of several DNA-peptide conjugates, through different bi-orthogonal conjugating methods. Chapter 1 explores the current literature and perspective for which this work is based. Chapter 2 discusses the synthesis of DNA by solid phase synthesis, before being modified with a maleimide based phosphoramidite. The chapter goes on to discuss the development of these methods. Commercially bought DNA was modified with two bi-functional crosslinkers, before being further modified with different peptides. The chapter discusses the full scale of method development to obtain DNA-peptide conjugates, including the first known example of DNA β turn conjugates in the literature.

Chapters 3-5 discusses the self-assembly of DNA-peptide conjugates, with peptide directed, DNA and peptide directed, and DNA directed self-assembly respectively. Chapter 3, peptide driven assembly is explored through the doping of the parent peptide ILVAGK with varying amounts of DNA-ILVAGK. These experiments were observed over 28 days, and the resultant structures analysed by atomic force microscopy. In Chapter 4, both peptide and DNA driven self-assembly of DNA-ILVAGK is studied through DNA hybridisation with complementary sequences of 1, 2, and 3 lengths. As in Chapter 3, these studies were supported by atomic force microscopy, dynamic light scattering and circular dichroism. The structures observed in Chapter 4 differed in timeline and type to those seen in Chapter 3. Chapter 5 investigates DNA driven self-assembly with the peptide assembly disabled using sodium dodecyl sulphate. The structures observed during 28 days of aging showed little change in morphology over the period. This is indicative of the presence of hierarchy within this system.

Chapter 6 consists of an overall conclusion, to draw together the individual conclusions drawn in each chapter.